There is a great deal of information regarding the minimal requirements for activation of primed T cells. T cell clones can be stimulated to release granule contents and produce lymphokines by anti-CD3 antibody or purified antigen-MHC proteins. T cell hybridomas can also be stimulated to produce lymphokines by anti-CD3 antibody or purified antigen-MHC proteins. Activation of these primed T cell lines can occur in the absence of specialized presenting cells and their accessory molecules. This project is to define the minimal requirements for activation of naive T cells and to evaluate the effects of additional stimuli on the magnitude and type of T cell activation elicited . We plan on evaluating the activation of naive T cells using different activators such as: anti-CD3 antibody, mitogens and purified allo-MHC molecules. We plan on evaluating different T cell activation parameters (lymphokine production, anergy induction, signal transduction and gene expression) in this system. We will then evaluate changes in these T cell responses caused by the addition of lymphokines, adhesion molecules or costimulatory molecules to the primary T cell stimulus.